Corticotropin-releasing factor (CRF) is involved in the acute anorexic effect of alpha-melanocyte-stimulating hormone: a study using CRF-deficient mice.
Alpha-melanocyte-stimulating hormone (alpha-MSH) and its receptors are critical and indispensable for maintaining appropriate feeding behavior and energy homeostasis in both mice and humans. Corticotropin-releasing factor (CRF) is a candidate for mediating the anorexic effect of alpha-MSH. In the present study, we examined whether CRF and its receptors are involved in the anorexic effect of alpha-MSH, using CRF-deficient (CRFKO) mice and a CRF receptor antagonist. Intracerebroventricular administration of NDP-MSH, a synthetic alpha-MSH analogue, suppressed food intake in wild-type (WT) mice. This effect was abolished by pretreatment with a non-selective CRF receptor antagonist, astressin, suggesting that the effect of alpha-MSH-induced anorexia was mediated by a CRF receptor. In CRFKO mice, administration with NDP-MSH did not affect food intake at an early phase (0-4h). In addition, CRF mRNA levels in the hypothalamus were significantly increased in NDP-MSH-treated mice. Therefore, our findings, using CRFKO, strongly support evidence that CRF is involved in the acute anorexic effect of alpha-MSH. On the other hand, NDP-MSH administered to CRFKO mice led to suppressed food intake at the late phase (4-12h), similar to the effect in WT mice. Further, NDP-MSH similarly reduced food intake during the late phase in all types of mice, including WT, CRFKO, and CRFKO with corticosterone replacement. The results would suggest that alpha-MSH-induced suppression of food intake at late phase was independent of glucocorticoids and CRF.
Kawashima
Shoko
S
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Sakihara
Satoru
S
Kageyama
Kazunori
K
Nigawara
Takeshi
T
Suda
Toshihiro
T
D000818:Animals; D000855:Anorexia / Q000188:drug therapy / Q000503:physiopathology; D003345:Corticosterone / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000494:pharmacology; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D010446:Peptide Fragments; C104416:astressin; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone